tbuckley/cabot-search huggingface dataset:
C-reactive protein in solid tumors: Clinically meaningful change and prognosis.
Authors: Wael Lasheen, Declan Walsh
Journal: Journal of Clinical Oncology (2023)

e15036 Background: C-Reactive Protein (CRP) has been associated with overall survival (OS) in both solid and hematologic malignancies. CRP is used alone or in conjunction with other variables e.g., albumin to create prognostic scores, yet use in clinical practice is limited. One barrier is the lack of guidelines quantifying clinically relevant changes. The aim of this study was to determine important changes in CRP and any association with OS. Methods: This was a retrospective cohort study of electronic medical record data. Subjects were included if they had a solid tumor, ≥2 CRP measurements post diagnosis, ≥7 days apart, age ≥18. They were divided into Baseline High CRP (HCRP≥10 mg/L), and Baseline Normal CRP (NCRP &lt; 10 mg/L) groups and analyzed separately. Median (range) and counts (%) were reported. Variables compared with parametric or nonparametric tests. CRP change (∆ = (2 nd CRP-1 st CRP)/1 st CRP) cut-off points were determined by Receiver Operator Curves or dividing groups into tertiles for sensitivity and specificity. We report the Kaplan-Meier survival plots and Cox Proportional Hazard Survival Models. Results: 4931 solid tumors were identified with CRP values; 1473 ≥2 CRP at least one week apart. N = 943 HCRP; N = 530 NCRP. HCRP were more likely to have gastrointestinal cancers, high white blood cell count, liver disease, metastatic disease, undergone surgery. NCRP were more likely breast or skin cancer, female, higher BMI, longer OS. 50% ↓ or 2-fold ↑ in CRP from baseline were statistically relevant cut-off points. In HCRP, estimated OS for ≥50% and &lt; 50% ↓ in CRP was, mean (SE), 87(2) and 81(4) months respectively; a six-month difference. In NCRP, estimated OS for ≥2 and &lt; 2-fold ↑ was 90(3) and 105(3) respectively; a fifteen-month difference. In the COX models, ≥ 50% CRP ↓ in HCRP was associated with 40% lower mortality risk; ≥ 2x CRP ↑ in NCRP was associated with 2-fold ↑ mortality risk. Conclusions: CRP level changes with cut-off points of either a 50% reduction or a 2-fold ↑ from baseline correlated with better and worse OS respectively, during follow up of solid tumors. This was both statistically and clinically important. CRP has the characteristics of an ideal tumor biomarker. This could aid in disease prognostication and impact treatment decision making in routine clinical practice. [Table: see text]
Association of adaptive immunity/inflammatory genes with survival in prostate cancer.
Authors: Austin Hopper, Harris Benjamin Krause, Andrew Elliott, Alex Patrick Farrell, Leisa Sutton, Pablo Tamayo, Hannah Carter, Ahmed Shabaik, Andrew Sharabi, Peter Kuhn, Elisabeth I. Heath, Emmanuel S. Antonarakis, Chadi Nabhan, Napoleone Ferrara, Fotis Asimakopoulos, Ida Deichaite
Journal: Journal of Clinical Oncology (2023)

5022 Background: Advances in immunotherapy have had little impact in prostate cancer (PCA). We have previously examined the immune microenvironment in both localized and metastatic PCA and found that primary PCA shows local inflammation/adaptive immunity whereas metastatic disease shows a shift towards immune suppression (Deichaite, 2022). Herein, we examine immune remodeling in PCA by evaluating changes in gene expression between localized and metastatic disease with heterogeneous treatment patterns in both primary and metastatic samples. Methods: Tumors from PCA (N = 5,419) were tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing of DNA (592-gene or whole exome) and RNA (whole transcriptome). Samples collected from the prostate gland (N = 3,284) or metastatic sites (N = 2,135) were analyzed. The Mann-Whitney U test was applied as appropriate, with P-values adjusted for multiple comparisons ( q &lt; .05). Real-world overall survival (OS) data was obtained from insurance claims and Kaplan-Meier estimates were calculated for molecularly defined subpopulations. Survival for tumors with high (-H) and low (-L) expression of genes of interest, defined as top and bottom quartile of expression (transcripts per million, TPM) across all tumors, was investigated. Differentially regulated pathways were assessed by gene set enrichment analysis (GSEA). Results: Compared to metastatic PCA, primary samples had increased median expression of pro-inflammatory genes IL-6 (1.2-fold), SELE (1.9-fold), NRK (6.3-fold), CEBPD (1.2-fold), NFKB2 (1.4-fold) and FOXP3 (1.4-fold) (each q &lt; .05). GSEA identified enrichment of E2F target genes in primary samples, while metastatic samples were enriched in inflammatory response, KRAS signaling and IL2/ STAT5 signaling pathways. The expression of inflammatory genes affected OS differently based on site. IL-6, NRK and SELE-H levels in primary samples were associated with increased OS. Within metastatic samples, CEBPD-H was associated with decreased OS and NFKB2-H was associated with an increased OS. FOSB-H was associated with increased OS in both primary and metastatic samples. Conclusions: We identify significant differences in the expression of inflammatory regulators and cytokines between localized and metastatic PCA tumors, which correlate with OS. These changes in the immune microenvironment can be leveraged for rational immunotherapy development and better targeted approaches. [Table: see text]
Impact of distance between tumor and nipple on survival outcomes in breast cancer.
Authors: Jong-Ho Cheun, Eunhye Kang, Jung Whan Chun, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Ki-Tae Hwang
Journal: Journal of Clinical Oncology (2023)

e12579 Background: Mastectomy is usually recommended surgical procedure for centrally located tumors regarding the increased risk of nipple invasion. Despite no difference in survival outcomes based on tumor locations, central tumor may have a higher chance of main lactiferous duct invasion, leading to tumor cell can migration to periphery of the breast. In this study, we investigated the relationship between locoregional recurrence (LRR) and the tumor-to-nipple distance (TND). Methods: We retrospectively analyzed the data of patients who underwent breast cancer surgery between 2004 and 2018 at two institutions. Patients who underwent neoadjuvant chemotherapy were excluded. TND was measured using preoperative MRI records. Results: A total of 9,014 patients were included, and median TND was 3.4 (0.0-15.0)cm. A restricted cubic spline curve showed that the hazard risk of LRR increased with shorter TND for all patients. While the risk of LRR appeared to apparently increase in the breast-conserving surgery (BCS) group, the mastectomy group showed the constant pattern. Thus, we conducted survival analysis for 5,455 patients who underwent BCS. We set the TND cutoff at 2.5 cm, which showed the lowest p-value for LRR rate. Compared to those with TND &gt; 2.5cm, patients with TND≤2.5cm had significantly lower rates of LRR (HR,1.83; 95%CI,[1.37-2.46], p &lt; 0.001) and distant metastasis (DM) (HR,1.53; 95%CI,[1.16-2.02], p = 0.002). However, overall survival was not different between the two groups (p = 0.405). Cox-regression analysis showed that TND still had a significant impact on LRR (HR,1.52; 95%CI,[1.11-2.09], p = 0.010) but not on DM. Importantly, TND still remained significant factor affecting LRR when analyzed as continuous variable (HR,1.04; 95%CI,[1.02-1.06], p &lt; 0.001). The prognostic impact of shorter TND was more evident in patients with high mammographic density. Conclusions: BCS can be considered a safe option for central tumors, but mastectomy could be a better choice for patients who are concerned about recurrence or unwilling to undergo additional surgeries.
P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for male and female adults and children with intermediate and poor-risk metastatic germ cell tumours (GCTs).
Authors: Danka Sinikovic Zebic, Ben Tran, Andrew James Martin, Farzana D. Pashankar, Danish Mazhar, Robert A Huddart, Matthew Wheater, Euan Thomas Walpole, Elaine Dunwoodie, Darren R. Feldman, Alison Jane Birtle, David Wyld, Nicola Jane Lawrence, Martin R. Stockler, Peter S. Grimison
Journal: Journal of Clinical Oncology (2023)

TPS5102 Background: Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for intermediate or poor risk metastatic GCT. Accelerating standard regimens by shortening the cycle length to 2-weekly improved cure rates in other cancers. P3BEP will determine effects of accelerated versus standard BEP in this setting. This is the first international, randomized trial of chemotherapy for intermediate and poor-risk metastatic GCT to include adults and children of both sexes. Methods: This open label, randomized, phase 3 trial is conducted seamlessly in 2-stages. The primary endpoint for stage I (n = 150) was favourable response; and for stage 2 (n = 500) is progression free survival at 2 years (PFS2y). These sample sizes provide &gt; 80% power with a 2-sided type I error rate of 5% to detect an absolute improvement of 21% in the favourable response rate (stage 1) and of 7% in the PFS2y (stage 2). The target population is males and females aged 11 to 45 with intermediate- or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomized (1:1) to 4 cycles of standard BEP (q3w) or accelerated-BEP (q2w) with cisplatin 20mg/m 2 D1-5, etoposide 100mg/m 2 D1-5, bleomycin 30 KIU weekly x 12, and pegylated G-CSF D6 or filgrastim daily (Figure 1). Study assessments occur at 30 days after completing chemotherapy, 6 months from randomisation, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour and blood samples are collected for translational substudies. Progress - As of Jan 2023, 241 participants have been recruited from 22 ANZ sites, 16 UK sites (led by Cambridge Clinical Trials Unit), and 55 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n = 76) identified no safety concerns. The stage I analysis of safety and activity (response rate) for the 1 st 150 patients was reviewed by the IDSMC, which recommended continuation of the trial as per protocol. Clinical trial information: NCT02582697 .
A single-arm, phase 2 clinical trial of abemaciclib in adult patients with recurrent grade 3 oligodendroglioma.
Authors: Stephen Joseph Bagley, Suyash Mohan, Seyed Ali Nabavizadeh, Thara Patel, Timothy Prior, Maikel Mansour, Emily Mccoy, Natalie Angeloni, Meghan O'Neill, Karen Albright, Suzanne Frangos, Caroline Blessing, Leah Coghlan, Eileen Maloney, Arati Suvas Desai
Journal: Journal of Clinical Oncology (2023)

2045 Background: Oligodendroglioma is a malignant glial neoplasm arising primarily in young adults. Although radiotherapy (RT) and chemotherapy result in durable disease control, tumor recurrence is inevitable and life-limiting. The cyclin D1-CDK4 axis is frequently dysregulated in recurrent oligodendroglioma. Abemaciclib is a selective CDK4/6 inhibitor that has been shown to achieve pharmacologically-relevant concentrations in brain tumor tissue. Methods: We conducted a single-center, single-arm, phase 2 trial evaluating the efficacy of abemaciclib in patients with recurrent oligodendroglioma, IDH-mutant and 1p/19q-codeleted, WHO Grade 3, following prior RT and ≥ 1 line of alkylating chemotherapy. Patients received abemaciclib 200mg twice daily. Primary endpoint was progression-free survival status at 6 months (PFS-6). Ten patients were needed for 80% power to detect the difference between the null (PFS-6 = 50%) and alternative (PFS-6 = 85%) hypotheses; one-sided α = 0.05. Modified RANO criteria were used for patients with enhancing tumors and RANO low-grade glioma criteria for patients with nonenhancing tumors. Results: Between November 2019 - August 2022, 10 patients were enrolled (Baseline Characteristics). Most common treatment-related adverse event (trAE) was grade 1-2 diarrhea, occurring in all 10 patients. Grade 3-4 trAEs included grade 4 thrombocytopenia (n=2), grade 3 neutropenia (n=1), grade 3 fatigue (n=2), and grade 3 ALT increase (n=1). In patients with enhancing tumor (n=9), best response was partial response in 2 patients (ORR=22.2%; DOR 13.1 and 7.7 months, respectively), stable disease (SD) in 3 patients (33.3%; duration of SD 17.0, 6.7, and 2.5 months, respectively), progressive disease in 3 patients (33.3%), and not evaluable in 1 patient (11.1%). In the patient with nonenhancing tumor, best response was SD (duration 10.2 months). Median PFS was 7.7 months (95% CI, 1.7 – 13.1 months); median overall survival was not reached (median follow-up 17 months). The study’s primary endpoint was not met; 5/10 patients (50%) were alive and progression-free at 6 months, below the minimum required (8/10) to consider abemaciclib worthy of further investigation. Conclusions: Despite objective responses and durable disease control in a small subset of patients, the efficacy of abemaciclib in recurrent grade 3 oligodendroglioma was not adequate to warrant further clinical evaluation of abemaciclib monotherapy in unselected patients. Correlative studies are ongoing to identify which patients with oligodendroglioma may benefit from abemaciclib. Clinical trial information: NCT03969706 . [Table: see text]
Health-related quality of life (HRQoL) of risk-based patient subgroups with advanced renal cell cancer (aRCC) treated with nivolumab plus cabozantinib (NIVO+CABO) vs sunitinib (SUN) in the CheckMate 9ER trial.
Authors: David Cella, Toni K. Choueiri, Steven I. Blum, Flavia Ejzykowicz, Joel Wallace, Joshua Zhang, Burcin Simsek, Cristina Ivanescu, Robert J. Motzer
Journal: Journal of Clinical Oncology (2023)

4527 Background: In CheckMate 9ER, NIVO+CABO improved or maintained HRQoL vs SUN in previously untreated aRCC. We report an exploratory analysis of HRQoL in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk-based subgroups treated with NIVO+CABO vs SUN in CheckMate 9ER (minimum follow-up, 36.5 mo). Methods: Subgroups were stratified by IMDC categories of favorable (F) risk (score = 0) or intermediate/poor (I/P) risk (score = 1–6) at randomization. HRQoL was evaluated using Functional Assessment of Cancer Therapy–Kidney Symptom Index (FKSI-19). Changes from baseline (BL) through wk 151 were analyzed using mixed-model repeated measures (MMRM). Bother due to treatment side effects (FKSI-19 item GP5) was assessed using a generalized estimating equations model (response dichotomized as minimal [“not at all” or “a little bit”] vs notable [“somewhat,” “quite a bit,” or “very much”]). Cox proportional hazards (CPH) modeling was used to evaluate time to confirmed deterioration (TTCD). Results: Differences in least square means (LSM) for FKSI-19 scores through wk 151 indicated HRQoL benefit in the NIVO+CABO arm over the SUN arm for I/P-risk patients (n = 505) but not for F-risk patients (n = 146). In the I/P-risk subgroup, longitudinal analysis of FKSI-19 total scores indicated that HRQoL improved through wk 151 in the NIVO+CABO arm but decreased from BL in the SUN arm. HRQoL declined from BL through wk 151 in F-risk patients in the NIVO+CABO and SUN arms. Patients were less likely to be bothered by side effects of NIVO+CABO vs SUN regardless of risk (I/P-risk odds ratio [OR], 0.50; 95% CI, 0.34–0.75; F-risk OR, 0.51; 95% CI, 0.28–0.91). TTCD analysis of FKSI-19 scores of the I/P-risk subgroup indicated that the NIVO+CABO arm had lower deterioration risk than the SUN arm. For the F-risk subgroup, risk based on FKSI-19 total scores was similar for both treatment arms. Conclusions: Compared with SUN, NIVO+CABO improved or maintained HRQoL in I/P-risk patients and had less side effect bother in all subgroups. There were no significant differences between treatment arms for F-risk patients. Clinical trial information: NCT03141177 . [Table: see text]
First-line envafolimab plus SOX chemotherapy for PD-L1 positive metastatic or recurrent gastric adenocarcinoma: A multi-centre, single-arm phase II clinical trial.
Authors: Zhu Liangjun
Journal: Journal of Clinical Oncology (2023)

e16029 Background: Clinical evidence for PD-L1 positive metastatic or recurrent gastric adenocarcinoma patients were relatively limited in clinic, which limited the development of evidence-based medicine for these patients. Immune checkpoint inhibitor (ICI) therapy has been established as the standard treatment for advanced gastric carcinoma patients recently. Envafolimab is the first approved subcutaneous single-domain PD-L1 antibody, which has been commercialized in China for the treatment of MSI-H/dMMR advanced solid tumors. This study aimed to investigate the efficacy and safety of Envafolimab plus SOX chemotherapy for metastatic or recurrent gastric adenocarcinoma, aiming to provide further reference for clinical rational drug use for this population. Methods: This multi-centre, single-arm, open-label study was conducted to evaluate the efficacy and safety of Envafolimab in metastatic or recurrent gastric adenocarcinoma. A total of 38 patients with histologically confirmed advanced gastric adenocarcinoma were enrolled. Patients will receive Envafolimab (300 mg, s.c., day 1) plus chemotherapy (oxaliplatin 130 mg/m 2 , i.v., day 1, and S-1 40mg, BSA＜1.25 m 2 、50mg 1.25 m 2 ＜BSA＜1.5 m 2 、60 mg BSA＞1.5m 2 , p.o., twice daily, days 1-14) every 3 weeks for 6 cycles, followed by maintenance treatment with Envafolimab plus S-1 until disease progression (PD), unacceptable toxicity, or patient refusal. Eligible patients must be histologically confirmed, advanced metastatic gastric adenocarcinoma or recurrent gastric adenocarcinoma after prior surgical treatment. Other key inclusion criteria were previously untreated, HER2-negative, PD-L1 positive (Combined Positive Score (CPS)≥1), ECOG performance status of 0 or 1, and adequate organ function. Patients with any prior ICI therapy, abnormal AFP elevation, or microsatellite-instability-high (MSI-H) status will be excluded. The primary endpoint was objective response rate (ORR) based on the RECIST version 1.1, and the secondary endpoints were progression-free survival (PFS), overall survival (OS), etc. Adverse events were evaluated using the CTCAE v5.0 criteria. Results: Overall, thirteen patients were consecutively enrolled from March, 2022 to September 2022 and involved in this study. The median age was 62.7 years. At present, eight patients were included for efficacy analysis, and nine for safety evaluation. The ORR was 50%, and DCR was 87.5%, based on RECIST v1.1. Survival data are not mature at present. The most common TRAEs were elevated AST (75%), elevated ALT (65%) and leukopenia (42.5%). No treatment-related deaths occurred. Conclusions: Envafolimab plus chemotherapy is a promising and tolerable therapeutic regimen for patients with metastatic or recurrent gastric adenocarcinoma. Clinical trial information: NCT05237349 .
Development and validation of prediction models for coexisting adnexa malignancy in patients with endometrial cancer using machine learning algorithm: A population-based cohort study.
Authors: Qiannan Wang, Kun Song
Journal: Journal of Clinical Oncology (2023)

e17617 Background: As the rate of ovarian conservation in endometrial cancer patients declined over the course of a decade, the study was to build and validate prediction models based on machine learning algorithms using preoperative predictors to evaluate the risk of coexisting adnexa malignancy, in order to guide decision-making for patients and clinicians before the surgery. Methods: Patients surgically treated for endometrial cancer from 30 medical center which forming the Chinese Endometrial Carcinoma Consortium (CECC) between 2010 and 2019 were enrolled. These patients were randomly divided at ratio of 7:3 into development cohort and validation cohort. Preoperative clinical and histopathological features were included as predictors, and least absolute shrinkage and selection operator (LASSO) was used for selecting candidate predictors. Machine learning (ML) algorithms including logistic regression (LR) analysis, support vector machine (SVM), random forest (RF), AdaBoost, decision tree (DT), naïve Bayes (NB), and multilayer perceptron (MP) were applied to develop the models. The best final model was selected by integrating area under the receiver operating characteristic curve (AUC) value as well as the relative sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy into account. Results: Among 3108 patients in the study cohort, 212 (6.7%) coexisted with adnexal malignancy. Data from 2226 female patients were divided into the cohort for model development. Ultimately the model included 10 predictors selected by LASSO: personal cancer history, age, CA-125, neutrophil lymphocyte ratio (NLR), tumor grade, myometrial involvement, cervix involvement, lymph node involvement, adnexal involvement, and extrauterine involvement. Among all ML algorithms, LR model outperformed the other algorithms, with an AUC of 80% and an accuracy of 85% in the validation cohort. Further evaluation proved that the model was well-calibrated and showed satisfied clinical utility. Based on LR, an online calculator was created for enhancing the clinical interpretability. Conclusions: This model provides individualized estimates of risk of adnexa malignancy in patients with endometrial cancer, with all model inputs available at the time before the surgery. A prospective feasibility study will be needed prior to implementation in the clinic.